tbuckley/cabot-search huggingface dataset:
Giant verruciform tumour on the penis
Authors: Rong Tao, Ruojun Wang
Journal: BMJ (2022)

<h3>Introduction</h3> Progesterone is an essential hormone involved in the process of implantation and pregnancy maintenance. Evidence from recent studies has supported the importance of serum progesterone level around the time of embryo transfer in hormonal replacement therapy frozen embryo transfer cycles and recommended the need for individualised luteal support. Low progesterone around the time of embryo transfer is found to be associated with decreased rate of pregnancy after frozen embryo transfer. This single-centre, longitudinal, randomised, interventional controlled study aims to compare the rate of ongoing pregnancy between two groups of women with progesterone level below 10 ng/mL on the day of frozen embryo transfer: the study group using 800 mg vaginal micronised progesterone supplemented with 50 mg intramuscular progesterone per day and the control group using only 800 mg vaginal micronised progesterone. <h3>Methods and analysis</h3> We enrol patients who are undergoing frozen embryo transfers with blastocyst-stage or cleavage-stage embryos and who satisfy the inclusion and exclusion criteria. After signing the informed consent, participants are randomised into two groups: the study group using vaginal micronised progesterone supplemented with progesterone intramuscular 50 mg per day and the control group using only vaginal micronised progesterone. Randomisation will be performed using R software at a 1:1 allocation ratio. Sequentially numbered, opaque sealed envelopes are used for allocation. The primary outcome is the rate of ongoing pregnancy. To demonstrate a difference of 10% with regard to rate of ongoing pregnancy, at least 370 participants per arm are required (type I error α=0.05, power=0.8). Assuming a dropout rate of 10%, a total of 824 patients (412 per group) will be invited. <h3>Ethics and dissemination</h3> This study was approved by the Ethics Committee of Tu Du Hospital on 17 May 2021 (reference number: 1251/QĐ-BVTD). All participants provide informed consent before being enrolled in the study. The results of our study will be submitted to reproductive medicine conferences and journals. <h3>Trial registration number</h3> NCT04897269.
Machine learning for real-time aggregated prediction of hospital admission for emergency patients
Authors: Zella King, Joseph Farrington, Martin Utley, Enoch Kung, Samer Elkhodair, Steve Harris, Richard Sekula, Jonathan Gillham, Kezhi Li, Sonya Crowe
Journal: npj Digital Medicine (2022)

Machine learning for hospital operations is under-studied. We present a prediction pipeline that uses live electronic health-records for patients in a UK teaching hospital's emergency department (ED) to generate short-term, probabilistic forecasts of emergency admissions. A set of XGBoost classifiers applied to 109,465 ED visits yielded AUROCs from 0.82 to 0.90 depending on elapsed visit-time at the point of prediction. Patient-level probabilities of admission were aggregated to forecast the number of admissions among current ED patients and, incorporating patients yet to arrive, total emergency admissions within specified time-windows. The pipeline gave a mean absolute error (MAE) of 4.0 admissions (mean percentage error of 17%) versus 6.5 (32%) for a benchmark metric. Models developed with 104,504 later visits during the Covid-19 pandemic gave AUROCs of 0.68-0.90 and MAE of 4.2 (30%) versus a 4.9 (33%) benchmark. We discuss how we surmounted challenges of designing and implementing models for real-time use, including temporal framing, data preparation, and changing operational conditions.
Runx3 drives a CD8+ T cell tissue residency program that is absent in CD4+ T cells
Authors: Raíssa Fonseca, Thomas N. Burn, Luke C. Gandolfo, Sapna Devi, Simone L. Park, Andreas Obers, Maximilien Evrard, Susan N. Christo, Frank A. Buquicchio, Caleb A. Lareau, Keely M. McDonald, Sarah K. Sandford, Natasha M. Zamudio, Nagela G. Zanluqui, Ali Zaid, Terence P. Speed, Ansuman T. Satpathy, Scott N. Mueller, Francis R. Carbone, Laura K. Mackay
Journal: Nature Immunology (2022)
Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics
Authors: Harry L. Horsnell, Robert J. Tetley, Henry De Belly, Spyridon Makris, Lindsey J. Millward, Agnesska C. Benjamin, Lucas A. Heeringa, Charlotte M. de Winde, Ewa K. Paluch, Yanlan Mao, Sophie E. Acton
Journal: Nature Immunology (2022)

Abstract Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular, physical, and structural properties and collectively determine tissue mechanics of lymph nodes, an immunologically relevant adult tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive expansion upon immune challenge. We find that in murine models of immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that C-type lectin-like receptor 2 (CLEC-2)–podoplanin signaling regulates the cell surface mechanics of fibroblasts, providing a mechanically sensitive pathway to regulate lymph node remodeling. Perturbation of fibroblast mechanics through genetic deletion of podoplanin attenuates T cell activation. We find that increased tissue tension through the fibroblastic stromal meshwork is required to trigger the initiation of fibroblast proliferation and restore homeostatic cellular ratios and tissue structure through lymph node expansion.
Study on the clinical indications for plasma as an alternative to the bronchoalveolar lavage fluid metagenomic next-generation sequencing test to detect consistent pathogens for septic patients in intensive care units
Authors: Ying Li, Gui-Yun Li, Dong-Xu Han, Yong-Wen Feng, Xiao-Min Liang, Di Ren, Li-Juan Yuan, Lin Zhang, Xin-Ke Meng, Jia-Ze Wang, Yu Ye, Jian-Peng Gao, Sha Wen, Yan-Hong Chen, Xi-Si He, Zhi-Ye Zou, Peng Han, Xiao-Hong Li, Hao-Bo Tu, Kai Lai, Mei Yang, Guan-Hua Rao, Shui-Qing Gui
Journal: Journal of Infection (2022)
Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling
Authors: Birgit Wilding, Dirk Scharn, Dietrich Böse, Anke Baum, Valeria Santoro, Paolo Chetta, Renate Schnitzer, Dana A. Botesteanu, Christoph Reiser, Stefan Kornigg, Petr Knesl, Alexandra Hörmann, Anna Köferle, Maja Corcokovic, Simone Lieb, Guido Scholz, Jens Bruchhaus, Markus Spina, Josef Balla, Biljana Peric-Simov, Jasmin Zimmer, Sophie Mitzner, Thomas N. Fett, Alexandra Beran, Lyne Lamarre, Thomas Gerstberger, Daniel Gerlach, Markus Bauer, Andreas Bergner, Andreas Schlattl, Gerd Bader, Matthias Treu, Harald Engelhardt, Stephan Zahn, Julian E. Fuchs, Johannes Zuber, Peter Ettmayer, Mark Pearson, Mark Petronczki, Norbert Kraut, Darryl B. McConnell, Flavio Solca, Ralph A. Neumüller
Journal: Nature Cancer (2022)
Optimize the combination regimen of Trastuzumab and Nab-paclitaxel in HER2-positive tumors via modulating Caveolin-1 expression by lovastatin
Authors: Canyu Yang, Shumin Fan, Xing Wang, Wei Liu, Long Yang, Bing He, Wenbing Dai, Hua Zhang, Xueqing Wang, Qiang Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2022)

The combination regimen of trastuzumab (Tras) plus Nab-paclitaxel (Nab) is recommended to treat HER2-positive (HER2+) cancers. However, they exert effects in different mechanisms: Tras need to stay on cell membranes, while Nab need to be endocytosed, therefore the concurrent combination regimen may not be the best one in HER2+ tumors treatment. Caveolin-1 (Cav-1) is a key player in mediating their endocytosis and is associated with their efficacy, but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy. Herein, we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+ Cav-1High tumor treatment. In the regimen, lovastatin (Lova) was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression, increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+ Cav-1High cells but not in HER2+ Cav-1Low cells. Therefore, by exchanging the dosing sequence of Nab and Tras, and by adding Lova at appropriate time points, the precise three-drug-sequential regimen (PTDS, Nab(D1)-Lova(D2)-Lova & Tras(D2+12 h)) was established. Compared with the concurrent regimen, the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+ Cav-1High tumors, which might be a promising combination regimen for these patients in clinics.
A Generalizable Evaluated Approach, Applying Advanced Geospatial Statistical Methods, to Identify High Lead Exposure Locations at Census Tract Scale: Michigan Case Study
Authors: Jianping Xue, Valerie Zartarian, Rogelio Tornero-Velez, Lindsay W. Stanek, Antonios Poulakos, Alan Walts, Kathy Triantafillou, Maryann Suero, Nicholas Grokhowsky
Journal: Environmental Health Perspectives (2022)

Despite great progress in reducing environmental lead (Pb) levels, many children in the United States are still being exposed.Our aim was to develop a generalizable approach for systematically identifying, verifying, and analyzing locations with high prevalence of children's elevated blood Pb levels (EBLLs) and to assess available Pb models/indices as surrogates, using a Michigan case study.We obtained ∼1.9 million BLL test results of children <6 years of age in Michigan from 2006-2016; we then evaluated them for data representativeness by comparing two percentage EBLL (%EBLL) rates (number of children tested with EBLL divided by both number of children tested and total population). We analyzed %EBLLs across census tracts over three time periods and between two EBLL reference values (≥5 vs. ≥10μg/dL) to evaluate consistency. Locations with high %EBLLs were identified by a top 20 percentile method and a Getis-Ord Gi* geospatial cluster "hotspot" analysis. For the locations identified, we analyzed convergences with three available Pb exposure models/indices based on old housing and sociodemographics.Analyses of 2014-2016 %EBLL data identified 11 Michigan locations via cluster analysis and 80 additional locations via the top 20 percentile method and their associated census tracts. Data representativeness and consistency were supported by a 0.93 correlation coefficient between the two EBLL rates over 11 y, and a Kappa score of ∼0.8 of %EBLL hotspots across the time periods (2014-2016) and reference values. Many EBLL hotspot locations converge with current Pb exposure models/indices; others diverge, suggesting additional Pb sources for targeted interventions.This analysis confirmed known Pb hotspot locations and revealed new ones at a finer geographic resolution than previously available, using advanced geospatial statistical methods and mapping/visualization. It also assessed the utility of surrogates in the absence of blood Pb data. This approach could be applied to other states to inform Pb mitigation and prevention efforts. https://doi.org/10.1289/EHP9705.
Reply to Paulius Bosas, Gintaras Zaleskis, and Dainius Characiejus’s Letter to the Editor re: Sylvia H.J. Jochems, Josef Fritz, Christel Häggström, Bengt Järvholm, Pär Stattin, Tanja Stocks. Smoking and Risk of Prostate Cancer and Prostate Cancer Death: A Pooled Study. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.03.033. Therapeutic Monitoring in Prostate Cancer Should Involve a Cotinine Test in Current Smokers
Authors: Sylvia H J Jochems, Pär Stattin, Tanja Stocks
Journal: European Urology (2022)
Expanding community engagement and advocacy in chronic viral hepatitis
Authors: Eneyi E Kpokiri, Dalia Elasi, Tiange P Zhang, Claire L Amon, Jessica Hicks, Jack Wallace, Philippa Easterbrook, Nick Walsh, Manal H El-Sayed, Philippa C Matthews, Su H Wang, Joseph D Tucker, Dan Wu
Journal: The Lancet. Gastroenterology & hepatology (2022)
Quality and Safety in Healthcare, Part XCII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2021)

Six Sigma is a methodology to diminish variation and errors and improve efficiency, quality, value, and profit, using certain defined steps and statistical analysis. For existing products and services, the DMAIC (Define, Measure, Analyze, Improve, and Control) acronym is used to stand for its steps. For new products and services, the Design for Six Sigma methodology is used. The goal of Six Sigma is to reduce the number of defects to no more than 3.4 for every million opportunities.
Reply to Zheng <i>et al</i>.
Authors: Bastian Eul, Michael Cekay, Khodr Tello, Jochen Wilhelm, Stefan Gattenlöhner, Ulf Sibelius, Friedrich Grimminger, Werner Seeger, Soni Savai Pullamsetti, Rajkumar Savai
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Leadership Diversity and Development in the Nation’s Cancer Centers
Authors: Caryn Lerman, Chanita Hughes-Halbert, Mary Falcone, David M Gosky, Roy A Jensen, Kelvin P Lee, Edith Mitchell, Kunle Odunsi, Jennifer W Pegher, Elisa Rodriguez, Yolanda Sanchez, Reuben Shaw, George Weiner, Cheryl L Willman
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract The capacity and diversity of the oncology leadership workforce has not kept pace with the emerging needs of our increasingly complex cancer centers and the spectrum of challenges our institutions face in reducing the cancer burden in diverse catchment areas. Recognizing the importance of a diverse workforce to reduce cancer inequities, the Association of American Cancer Institutes conducted a survey of its 103 cancer centers to examine diversity in leadership roles from research program leaders to cancer center directors. A total of 82 (80%) centers responded, including 64 National Cancer Institute–designated and 18 emerging centers. Among these 82 respondents, non-Hispanic White individuals comprised 79% of center directors, 82% of deputy directors, 72% of associate directors, and 72% of program leaders. Women are underrepresented in all leadership roles (ranging from 16% for center directors to 45% for associate directors). Although the limited gender, ethnic, and racial diversity of center directors and perhaps deputy directors is less surprising, the demographics of current research program leaders and associate directors exposes a substantial lack of diversity in the traditional cancer center senior leadership pipeline. Sole reliance on the cohort of current center leaders and leadership pipeline is unlikely to produce the diversity in cancer center leadership needed to facilitate the ability of those centers to address the needs of the diverse populations they serve. Informed by these data, this commentary describes some best practices to build a pipeline of emerging leaders who are representative of the diverse populations served by these institutions and who are well positioned to succeed.
The burden of prolonged smell and taste loss in covid-19
Authors: NKW Tan, CJ Tan, BKJ Tan, R Han, JJ Zhao, ESH Quah, C Kelly, NWY Teo, A See, ST Toh, C Hopkins
Journal: BMJ (2022)

It was sudden, like turning an electric switch off."This is how one patient described her abrupt loss of smell and taste following infection with covid-19."I was eating some lunch on day three after contracting covid-19 and one moment I could still smell and taste the flavours of my soup, and the next everything vanished."She was not alone in this.In fact, smell and taste loss are common complaints among patients with covid-19, with an estimated 50% of patients reporting these symptoms. 1This is thought to occur due to conductive barriers and nerve damage from the extensive inflammation in covid-19 infection. 2 -5 The recovery of smell and taste is very much a gradual process for some.In our analysis of 3699 patients from 12 countries, recently published in The BMJ, we found that at the 30 day mark following the initial infection, only 74% and 79% of patients are expected to recover their smell and taste respectively. 6ecovery rates rise with each passing month, reaching a peak of 96% for smell and 98% for taste after six months.Using a mathematical technique known as cure modelling to project the plateaus of smell and taste recovery across 18 studies, we found that self-reported smell loss may persist in 5.6% of patients, while 4.4% may not recover their self-reported sense of taste (for some this reflects loss of flavour perception, a function of olfaction, while in others it may reflect true gustatory dysfunction). 7ith more than 550 million confirmed covid-19 cases as of July 2022, this means that potentially 15 million and 12 million patients may experience long term smell and taste impairments, respectively, based on our modelling.This could contribute to the rising burden of long covid.Furthermore, self-reporting may over estimate recovery, 7 suggesting that the true burden of olfactory dysfunction is even greater.
Patient outcomes following emergency admission to hospital for COVID-19 compared with influenza: retrospective cohort study
Authors: Thomas Woodcock, Geva Greenfield, Ajit Lalvani, Azeem Majeed, Paul Aylin
Journal: Thorax (2022)

Background We examine differences in posthospitalisation outcomes, and health system resource use, for patients hospitalised with COVID-19 during the UK’s first pandemic wave in 2020, and influenza during 2018 and 2019. Methods This retrospective cohort study used routinely collected primary and secondary care data. Outcomes, measured for 90 days follow-up after discharge were length of stay in hospital, mortality, emergency readmission and primary care activity. Results The study included 5132 patients admitted to hospital as an emergency, with COVID-19 and influenza cohorts comprising 3799 and 1333 patients respectively. Patients in the COVID-19 cohort were more likely to stay in hospital longer than 10 days (OR 3.91, 95% CI 3.14 to 4.65); and more likely to die in hospital (OR 11.85, 95% CI 8.58 to 16.86) and within 90 days of discharge (OR 7.92, 95% CI 6.20 to 10.25). For those who survived, rates of emergency readmission within 90 days were comparable between COVID-19 and influenza cohorts (OR 1.07, 95% CI 0.89 to 1.29), while primary care activity was greater among the COVID-19 cohort (incidence rate ratio 1.30, 95% CI 1.23 to 1.37). Conclusions Patients admitted for COVID-19 were more likely to die, more likely to stay in hospital for over 10 days and interact more with primary care after discharge, than patients admitted for influenza. However, readmission rates were similar for both groups. These findings, while situated in the context of the first wave of COVID-19, with the associated pressures on the health system, can inform health service planning for subsequent waves of COVID-19, and show that patients with COVID-19 interact more with healthcare services as well as having poorer outcomes than those with influenza.
No<i>H. pylori</i>, no adenocarcinoma for patients with autoimmune gastritis
Authors: James Goldenring
Journal: Gut (2022)

<h3>Introduction</h3> The risk of cardiovascular outcomes associated with gestational hypertension is unclear. This study aimed to quantify the association between gestational hypertension and cardiovascular outcomes for women. <h3>Design</h3> Systematic review and meta-analysis. Data Sources PubMed, Embase and Web of Science. Eligibility Criteria Studies examining the association between gestational hypertension and any cardiovascular outcome, including cardiovascular disease, coronary heart disease, stroke and heart failure. Two reviewers independently assessed the abstracts and full-text articles. Study characteristics and the relative risk of cardiovascular outcomes associated with gestational hypertension were extracted from eligible studies. Where appropriate, estimates were pooled with inverse variance weighted random-effects meta-analysis, and the absolute risk increases were calculated using the European population as a reference, as the majority of studies came from Europe. <h3>Results</h3> Nineteen studies involving 3,601,192 women (128,445 with gestational hypertension) were identified. A history of one or more pregnancies affected by gestational hypertension was associated with an increased risk of cardiovascular disease (12 studies, relative risk 1.73, 95% confidence interval: 1.43–2.08), coronary heart disease (8 studies, 1.56, 1.35–1.81) and heart failure (4 studies, 1.70, 1.43–2.02). (See Figure) There was also evidence for an increased risk of stroke (9 studies, 1.66, 0.99–2.80). Among the outcomes examined, the highest absolute risk increase was for cardiovascular disease: 14.0 events/1000 person-years. Associations between gestational hypertension and cardiovascular disease were broadly consistent across subgroups, although there was evidence that high quality studies with a low risk of bias had lower effect estimates. When analyses were restricted to high quality studies, an increased risk was found for all outcomes: cardiovascular disease, (1.53, 1.25–1.88); coronary heart disease, (1.40, 1.26–1.54); stroke, (1.35, 1.14–1.60); and heart failure, (1.70, 1.43–2.02). <h3>Conclusion</h3> Gestational hypertension is associated with an increased risk of overall cardiovascular disease, coronary heart disease, stroke and heart failure. Only two studies evaluated risk associated with the number of pregnancies affected by gestational hypertension, therefore more research is needed to assess the presence of a dose-response relationship. <h3>Conflict of Interest</h3> None
Smell and taste dysfunction after covid-19
Authors: Paolo Boscolo-Rizzo, Jerry Polesel, Luigi A Vaira
Journal: BMJ (2022)

Objective: The glucagon gene (Gcg) encodes preproglucagon, which is cleaved to form glucagon-like peptide 1 (GLP1) and other mature signaling molecules implicated in metabolic functions. To date there are no transgenic rat models available for precise manipulation of GLP1-expressing cells in the brain and periphery. Methods: To visualize and manipulate Gcg-expressing cells in rats, CRISPR/Cas9 was used to express iCre under control of the Gcg promoter. Gcg-Cre rats were bred with tdTomato reporter rats to tag Gcg-expressing cells. Cre-dependent AAVs and RNAscope in situ hybridization were used to evaluate the specificity of iCre expression by GLP1 neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt), and by intestinal and pancreatic secretory cells. Food intake was assessed in heterozygous (Het) Gcg-Cre rats after chemogenetic stimulation of cNTS GLP1 neurons expressing an excitatory DREADD. Results: While genotype has minimal effect on body weight or composition in chow-fed Gcg-Cre rats, homozygous (Homo) rats have lower plasma glucose levels. In neonatal and adult Gcg-Cre/tdTom rats, reporter-labeled cells are present in the cNTS and IRt, and in additional brain regions (e.g., basolateral amygdala, piriform cortex) that lack detectable Gcg mRNA in adults but display transient developmental or persistently low Gcg expression. Compared to wildtype (WT) rats, hindbrain Gcg mRNA and GLP1 protein in brain and plasma are markedly reduced in Homo Gcg-Cre rats. Chemogenetic stimulation of cNTS GLP1 neurons reduced overnight chow intake in males but not females, the effect in males was blocked by antagonism of central GLP1 receptors, and hypophagia was enhanced when combined with a subthreshold dose of cholecystokinin-8 to stimulate gastrointestinal vagal afferents. Conclusions: Gcg-Cre rats are a novel and valuable experimental tool for analyzing the development, anatomy, and function of Gcg-expressing cells in the brain and periphery. In addition, Homo Gcg-Cre rats are a unique model for assessing the role of Gcg-encoded proteins in glucose homeostasis and energy metabolism.